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The William Harvey Research Institute - Barts and The London

Professor Alberto Mantovani

Alberto

Chair of Inflammation and Therapeutic Innovation

Centre: Experimental Medicine and Rheumatology

Email: a.mantovani@qmul.ac.uk

Profile

ORCID iD: https://orcid.org/0000-0001-5578-236X


Alberto Mantovani, MD, is Emeritus Professor of Pathology at the Humanitas University in Milan, and Scientific Director of the Istituto Clinico Humanitas.  His attention has been focused on molecular mechanisms of innate immunity and inflammation. He has contributed to the advancement of knowledge in the field of Immunology formulating new paradigms and identifying new molecules and functions.

For his research activity he received several Italian and international awards, such as the Triennial OECI Award from the Organization of the European Cancer Institutes,  the Robert Koch Award for his contribution to tumor immunology and immunotherapy, the American-Italian Cancer Foundation (AICF) Prize for Excellence in Medicine and the American Association for Cancer Research International Pezcoller Award for Extraordinary Achievement in Cancer Research. The broad impact of his contributions is testified by citations.  As of October 2020 he has over 129,000 citations and an H-index of 168 (Scopus).  

Selected major honors

National or International awarded in Italy

1998: Biotec Award
2004: Guido Venosta Award for Cancer Research by the President of the Republic of Italy
2005: Premio Ippocrate per la Ricerca Biomedica
2006: “Onorificenza al Merito della Repubblica Italiana”  (Commendatore, knightwood equivalent) for scientific contribution by the President of  the Republic of Italy
2007: Galileo Galilei Prize for Research in Biomedical Sciences (International Jury)
2012: Premio Nazionale "L'Altra Italia ... Vite da Premio"
2014: Premio Rosa Camuna 2014, Regione Lombardia
2015: Ferrari-Soave International Prize, Accademia delle Scienze, Torino.
2016: NIBIT Award, Siena
2016: Premio Roma allo Sviluppo del Paese.
2016: International Feltrinelli Prize from the Accademia dei Lincei.
2017: Premio Scanno, Fondazione Tanturri, Scanno, Italy.
2018: Medaglia d’Oro di Benemerenza Civica, Milan Municipality (Ambrogino d’Oro).

International

2000: Marie T. Bonazinga Award, Society for Leukocyte Biology, Boston, USA
2006: European Federation of Immunological Societies – Schering Plough, 1st European Immunology Prize, Paris, France
2009: William Harvey Award, Oustanding Scientist 2009, London, UK.
2015: European Society for Clinical Investigation Albert Struyvenberg Medal
2015: The Milstein Award for Excellence in Interferon and Cytokine Research, International Cytokine & Interferon Society. 
2016: OECI (Organization of European Cancer Institutes) Prize for contribution to Cancer Immunology and Immunotherapy. OECI awards the OECI Prize every three years.
2016: Robert Koch Award, Robert Koch Stiftung, Germany
2017:  Journal of Autoimmunity dedicated Issue to Alberto Mantovani
2018: American-Italian Cancer Foundation (AICF, New York) Prize for Excellence in Medicine.
2019: American Association for Cancer Research International Pezcoller Award for Extraordinary Achievement in Cancer Research.
2019:  ITOC6 – 6th Immunotherapy of Cancer Conference Lifetime Achievement Award

Selected memberships, boards and academies

1995-1998: President, Italian Federation of Immunological Societies
1998-2001: President, Italian Society of Immunology
2000 to date: European Molecular Biology Organization (EMBO) Member
2002: Member, The Henry Kunkel Society
2005-2010: Board Member of the Global Alliance for Vaccines and Immunization (GAVI Alliance)
2008: Member, Faculty of 1000 Biology
2009-2010: President, International Cytokine Society
2011-2013: Board Member, International Union of Immunological Societies (IUIS)
2013-2016: Vice-President/President Elect, International Union of Immunological Societies (IUIS)
2016: Member, Accademia dei Lincei, Rome, Italy
2016: Member, Robert Koch Stiftung, Berlin                                                     
2016-2019: President, International Union of Immunological Societies (IUIS)
2017: Member, Academia Europaea
2017: Honorary Member, Scandinavian Society of Immunology

Research

Tumor-associated macrophages (TAM)
Demonstration in the late ‘70s of the protumor function of tumor-associated macrophages  (TAM, an acronym now generally used and coined by him in the ‘70s)  linking inflammation and cancer (reviewed in Balkwill and Mantovani, Lancet, 2001). TAM as an M2-like population (Bottazzi et al, Science 1983; Mantovani et al., Nature 2008; Balkwill et al., Cancer Cell 2005).  Promotion of tumor progression by IL-1 (Cancer Res. 1990; 1993). First linking of a genetic event (RET/PTC rearrangement)  causing cancer in humans to the construction of an inflammatory microenvironment (Borrello et al., PNAS 2005). Proof of principle that targeting tumor promoting macrophages has therapeutic value in humans (Germano et al, Cancer Cell 2013). Demonstration that PTX3 is an extrinsic oncosuppressor regulating Complement and macrophage-driven tumor promoting inflammation (Bonavita et al Cell 2015). Discovery of a novel pathway of anti-tumor immunity involving neutrophils, macrophages and unconventional, double negative T cells (Ponzetta et al, Cell 2019). Alberto Mantovani is recognized among his peers as a forerunner in the ‘70s and a “founding father” of the renaissance of the inflammation-cancer connection. For IL-1R8, see below, IL-1.

Chemokines
Description and role in TAM recruitment of a unique monocyte attractant, Monocyte Chemotactic Protein-1 (CCL2), as tumor-derived chemotactic factor (Bottazzi et al, Science 1983). Characterization of chemokines and role in pathophysiology, including dendritic cell and polarized T cell migration. Induction of chemokine production by IL-6 in endothelial cells via trans-signaling, a key component of chronic inflammation and cancer (Romano et al, Immunity 1997). Characterization of D6 as a decoy receptor for inflammatory CC chemokines (Mantovani et al, Nature Rev. Immunol 2006). Role of chemokines in carcinogenesis (for a recent contribution Bonavita et al Cell 2015).

IL-1/Toll-like receptors (TLR)
Endothelial cell activation by IL-1 and cytokines (Rossi et al., Science 1985; Bussolino et al, Nature 1989; Romano et al, Immunity 1997). Identification of the type II receptor as a decoy receptor, a novel concept in biology (Colotta et al, Science 1993); the discovery of a decoy receptor represented a paradigm shift after the original definition of the concept of “receptor” by Langley in the 1930’; decoy receptors are now recognized as a general,  evolutionary conserved strategy to tune cytokines, chemokines and growth factors. Cloning of an intracellular isoform of the IL-1 receptor antagonist (Muzio et al., J. Exp. Med.  1995). First demonstration of MyD88 as the adaptor of mammalian Toll-Like Receptors (TLR) and identification of downstream transducers (Muzio et al., J. Exp. Med. 1998). Cloning and characterization of TIR8/SIGIRR (IL-1R8), a negative regulator of IL-1 receptor and TLR signalling (Garlanda et al, Immunity 2013; 2019). Role in carcinogenesis. In NK cells IL-1R8 serves as a checkpoint: its blocking unleashes resistance to carcinogenesis and metastasis at selected anatomical sites (Molgora et al, Nature 2017).

Humoral innate immunity
Cloning (cDNA and genomic, mouse and human), structural and functional characterization of the first long pentraxin PTX3 as an IL-1 inducible gene (Garlanda et al, Nature 2002; Jeannin et al, Immunity 2005; Jaillon et al. J. Exp Med 2007 ; Deban et al, Nature Immunol. 2010; Jaillon et al. Immunity 2014; Bonavita et al. Cell 2015); structural immunobiology; role as a paradigm for humoral innate immunity; role as an extrinsic oncosuppresor in murine and human tumors regulating Complement and macrophage driven tumor promoting inflammation (Bonavita et al. Cell 2015); diagnostic and therapeutic translation (Cunha et al New England J. Med. 2014; ongoing). Thus, a regulator of macrophage-driven tumor promoting inflammation is a bona fide cancer gene, silenced in selected human tumors such as colorectal cancer, a finding now independently confirmed in large patients cohorts. 

Activity at WHRI 
Since joining WHRI, Alberto Mantovani engaged in collaborative interactions with members of the Faculty (grant applications; exchange of postdocs; mentoring Early Career Researchers; publications). In particular, a long standing interaction with Frances Balkwill was reestablished (see above).  In collaboration with Costantino Pitzalis, the relevance of a panel of molecules discovered and/or characterized by Alberto Mantovani to rheumatoid arthritis is being explored.  As an example, the expression and function of the macrophage tetraspan-like molecule MS4A4A was defined (Mattiola et al, Nature Immunol 2019).  Its significance in pathogenesis and as a biomarker is currently being investigated.

Key Publications

Originals

  • Donadon M, Torzilli G, Cortese N, Soldani C, Di Tommaso L, Franceschini B, Carriero R, Barbagallo M,Rigamonti A, Anselmo A, Colombo FS, Maggi G, Lleo A, Cibella J, Peano C, Kunderfranco P, Roncalli M, Mantovani A*, Marchesi F* (*corresponding authors). Macrophage morphology as a correlate of functional diversity with prognostic significance in colorectal liver metastasis. J. Exp Med. 2020 Nov 2; 217(11): e20191847. doi: 10.1084/jem.20191847.
  • Ponzetta A, Carriero R, Carnevale S, Barbagallo ML, Molgora M, Perucchini C, Magrini E, Gianni F, Kunderfranco P, Polentarutti N, Pasqualini F, Di Marco S, Supino D, Peano C, Cananzi F, Colombo P, Pilotti S, Alomar SY, Bonavita E, Galdiero MR, Garlanda C, Mantovani A*, Jaillon S* (*corresponding authors). Neutrophils driving unconventional T cells mediate resistance against murine sarcomas and selected human tumors. Cell, 178(2):346-360, 2019.
  • Mattiola I, Tomay F, De Pizzol M, Silva-Gomes R, Savino B , Gulic T, Doni A , Lonardi S , Boutet MA , Nerviani A, Carriero R , Molgora M , Stravalaci M, Morone D, Shalova IN, Lee Y, Biswas SK, Mantovani G, Sironi M, Pitzalis C, Vermi W, Bottazzi B, Mantovani A*, Locati M* (*corresponding authors).  The interplay of the macrophage tetraspan MS4A4A with Dectin-1 and its role in NK cell-mediated resistance to metastasis.  Nature Immunol, 20(8):1012-1022, 2019.
  • Molgora M, Bonavita E, Ponzetta A, Riva F, Barbagallo M, Jaillon S, Popovic B, Bernardini G, Magrini E, Gianni F, Zelenay S, Jonjic S, Santoni A, Garlanda C, Mantovani A. IL-1R8 is a checkpoint in NK cells regulating anti-tumor and anti-viral activity. Nature, 551:110-114, 2017.
  • Doni A, Musso T, Morone D, Bastone A, Zambelli V, Sironi M, Castagnoli C, Cambieri I, Stravalaci M, Pasqualini F, Laface I, Valentino S, Tartari S, Ponzetta A, Maina V, Barbieri SS, Tremoli E, Catapano AL, Norata GD, Bottazzi B, Garlanda C, Mantovani A. An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode. J Exp Med.  212: 905-925, 2015.
  • Bonavita E, Gentile S, Rubino M, Maina V, Papait R, Kunderfranco P, Greco C, Feruglio F, Molgora M, Laface I, Tartari S, Doni A, Pasqualini F, Barbati E, Basso G, Galdiero MR, Nebuloni M, Roncalli M, Colombo PG, Laghi L, Lambris JD, Jaillon S, Garlanda C, Mantovani A.  PTX3 is an extrinsic oncosuppressor regulating complement-dependent inflammation in cancer. Cell  160: 700-714, 2015.
  • Jaillon S,  Moalli F,  Ragnarsdottir B, Bonavita E, Riva F, Barbati E, Nebuloni M, Krajinovic LC, Markotic A, Valentino S, Doni A, Tartari S, Graziani G, Montanelli A, Delneste Y, Svanborg C, Garlanda C, Mantovani A.  The humoral pattern recognition molecule PTX3 is a key component of innate immunity against urinary tract infection. Immunity 40: 621-632, 2014.
  • Cunha C, Aversa F, Lacerda JF, Busca A, Kurzai O, Grube M, Löffler J, Maertens JA,  Bell AS, Inforzato A, Barbati E, Almeida B, Santos e Sousa P, Barbui A, Potenza L, Caira M, Ph.D., Rodrigues F, Salvatori G, Pagano L, Luppi M, Mantovani A,Velardi A, Romani L, Carvalho A.  Genetic deficiency of PTX3 and aspergillosis in stem cell transplantation. New Engl J Med, 370:421-432, 2014.
  • Germano G, Frapolli R, Belgiovine C, Anselmo A, Pesce S, Liguori M, Erba E, Uboldi S, Zucchetti M, Pasqualini F, Nebuloni M, van Rooijen N, Mortarini R, Beltrame L, Marchini S, Fuso Nerini I, Sanfilippo R, Casali PG, Pilotti S, Galmarini CM, Anichini A, Mantovani A, D'Incalci M, Allavena P. Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell 23: 249-262, 2013.
  • Deban L, Castro Russo R, Sironi M, Moalli F, Scanziani M, Zambelli V, Cuccovillo I, Bastone A, Gobbi M, Valentino S, Doni A, Garlanda C, Danese S, Salvatori G, Sassano M, Evangelista V, Rossi B,  Zenaro E, Constantin G, Laudanna C, Bottazzi B, Mantovani A  Regulation of leukocyte recruitment by the long pentraxin PTX3.  Nature Immunol, 11: 328-334, 2010.
  • Di Liberto D, Locati M, Caccamo N, Vecchi A, Meraviglia S, Salerno A, Sireci G, Nebuloni M, Cardona P-J, Dieli F, Mantovani A.  Role of the chemokine decoy receptor D6 in balancing inflammation, immune activation and antimicrobial resistance in Mycobacterium tuberculosis infection.  J. Exp. Med. 205: 2075-2084, 2008.
  • Lech M,Kulkarni OP, Pfeiffer S, Savarese E, Krug A, Garlanda C, Mantovani A, Anders H-J  Tir8/Sigirr prevents murine lupus by suppressing the immunostimulatory effects of lupus autoantigens.  J. Exp. Med. 205: 1879-1888, 2008.
  • Jaillon S, Peri G, Delneste Y, Frèmaux I, Doni A, Moalli F, Garlanda C, Romani L, Gascan H, Bellocchio S, Bozza S, Cassatella MA, Jeannin P, Mantovani A.  The humoral pattern recognition receptor PTX3 is stored in neutrophil granules and localized in extracellular traps.   J. Exp. Med., 204, 793-804, 2007.
  • Martinez de la Torre Y, Buracchi C, Borroni EM, Dupor J,  Bonecchi R, Nebuloni M, Pasqualini F, Doni A, Lauri E et al.  Protection against inflammation- and autoantibody- caused fetal loss by the chemokine decoy receptor D6. PNAS 104:2319-2324, 2007
  • Biswas SK, Gangi L, Paul S, Schioppa T, Saccani A, Sironi M, Bottazzi B, Doni A, Vincenzo B, Pasqualini F, Vago L, Nebuloni M, Mantovani A*, Sica A. (* corresponding author). A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation). Blood 107:2112-2122, 2006.
  • Borrello MG, Alberti L, Fischer A, Degl’InnocentiD, Ferrario C, Gariboldi M, Marchesi F, Allavena P, Greco A, Collini P, Pilotti S, Cassinelli G, Bressan P, Fugazzola L, Mantovani A*, Pierotti M*  (*corresponding authors).  Induction of a proinflammatory programme in normal human thyrocytes by the RET/PTC1 oncogene.  PNAS, 102:  14825-14830, 2005.
  • Jeannin P., Bottazzi B., Sironi M., Doni A., Rusnati M., Presta M., Maina V., Magistrelli G., Haeuw J.F., Hoeffel G., Thieblemont N., Corvaia N., Garlanda C., Delneste Y., Mantovani A.  Complexity and complementarity of outer membrane protein-A recognition by cellular and humoral innate immunity receptors  Immunity 22: 551-560, 2005. 

Reviews

  • Mantovani A, Netea M Trained Innate Immunity, epigenetics, and Covid-19.  New Engl J Med. 383(11):1078-1080, 2020.
  • Locati M, Curtale G, Mantovani A Diversity, mechanisms and significance of macrophage plasticity. Annu. Rev. Pathol 15: 123-147, 2020.
  • Jaillon S, Ponzetta A, Di Mitri D, Santoni A, Bonecchi R, Mantovani A.  Neutrophil diversity and plasticity in tumour progression and therapy. Nat Rev. Cancer 20(9): 485-503, 2020.
  • Mantovani A, Dinarello CA, Molgora M, Garlanda C. IL-1 and related cytokines in innate and adaptive immunity in health and disease. Immunity  50(4):778-795, 2019.
  • Mantovani A., Marchesi F., Laghi L., Malesci A., Allavena P.   Tumor-associated macrophages as treatment targets in oncology. Nature Rev, Clin. Oncol. 14(7):399-416, 2017.
  • Mantovani A, Allavena P. The interaction of anticancer therapies with tumor-associated macrophages.J Exp Med. 2015 Apr 6;212(4):435-445.
  • Garlanda C., Dinarello C.A.,  Mantovani A. The IL-1 family: back to the future. Immunity 39: 1003-1018, 2013.
  • Locati M.,  Mantovani A., Sica A. Macrophage activation and polarization as an adaptive component of innate immunity. Adv. Immunol. 120: 163-184, 2013
  • Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest. 122: 787-795, 2012.
  • Biswas S.K. and  Mantovani A. Orchestration of metabolism by macrophages. Cell Metab. 15: 432-437, 2012.
  • Mantovani A, Cassatella MA, Costantini C, Jaillon S. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol. 11: 519-531, 2011.
  • Biswas S.K. and  Mantovani A.  Macrophage plasticity and interaction with lymphocyte subsets: cancer as paradigm. Nat Immunol 11: 889-896, 2010.
  • Bottazzi B, Doni A, Garlanda C, Mantovani A. An Integrated View of Humoral Innate Immunity: Pentraxins as a Paradigm. Annu Rev Immunol. 28:157-183, 2010.
  • Garlanda C, Anders HJ, Mantovani A.TIR8/SIGIRR: an IL-1R/TLR family member with regulatory functions in inflammation and T cell polarization.Trends Immunol. 30: 439-446, 2009.
  • Mantovani A. Cancer: Inflaming metastasis. Nature 45: 36-37, 2009.
  • Mantovani A, Allavena P, Sica A, Balkwill F  Cancer-Related Inflammation. Nature 454: 436-444, 2008.
  • Mantovani, A., Romero, P., Paluka, AK., Marincola, FM.  Tumor immunity: effector response to tumor and the influence of the microenvironment. Lancet 371:771-783, 2008.
  • Mantovani A, Bonecchi R, Locati M.  Tuning inflammation and immunity by chemokine sequestration: decoys and more. Nature Rev. Immunol. 6: 907-918, 2006.
  • Balkwill F, Charles KA, Mantovani A. Smouldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 7: 211-217, 2005.
  • Garlanda C.,  Bottazzi B., Bastone A.,  Mantovani A., Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility Annu. Rev. Immunol., 23: 337-366, 2005.

News

Contribution to Public Awareness  of Science

Alberto Mantovani has been actively involved in the fostering of science and scientific policies in Italy at various levels, with a focus on Immunology, Vaccines, Oncology and Public Health, taking public stands on several issues  including quackery whenever appropriate. He regularly contributes to the most authoritative italian daily newspapers (eg Corriere della Sera; La Repubblica; La Stampa; Il Sole 24 Ore) and magazines (Espresso and Panorama). As of January 2020 he has been at the forfront in raising public awareness of Covid-19. He wrote five books on Immunology and Science targeted to the lay public (I Guardiani della Vita, Baldini e Castoldi, 2011; Immunità e Vaccini, Mondadori, 2016;  Non avere Paura di Sognare, La Nave di Teseo, 2016; Bersaglio Mobile, Mondadori, 2018; Il Fuoco Interiore. Immunità e malattie, Mondadori 2020). He contributed to scientific (eg SuperQuark; TGR Leonardo; Radiotre Scienza; Sapiens) and general radio and television (eg Geo; Che Tempo che Fa; general national news) programs. To promote science awareness and policy together with astrophysicist Tommaso Maccacaro he founded the website http://www.scienzainrete.it. He represented Accademia dei Lincei in the European Academies Science Advisory Council (EASAC) working group on homeopathy and in the formulation of the final EASAC statement on it. Together with Guido Forni, Lorenzo Moretta and Giovanni Rezza he wrote the position paper “Vaccines. A position paper from the Accademia Nazionale dei Lincei” (2018). A revised version is now published as a book with a section on Covid-19 (I vaccini fanno bene. Perchè dobbiamo credere nella scienza per difenderci da virus e batteri; La Nave di Teseo, 2020). Together with Maurizio Cecconi and Guido Forni on behalf of the Health Commission of the Accademia dei Lincei he prepared and updates a report on COVID-19

https://www.lincei.it/sites/default/files/documenti/Commissioni/Health_committee_Covid19_Summer_report_July2020.pdf